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332 citation(s) found for "Jacobs, B".

SARS-CoV-2 Viremia Is Associated with Lower Respiratory Tract Viral Load and Plasma Markers of Epithelial Injury and Thrombin Generation in Critically Ill Patients
Bittner, M.J., Jacobs, Jordan, Naqvi, Asma , Meyer, Michael, Methé, Barbara A. , Neal, M. , Lee, J., Morris, Alison , McVerry, Bryan J , Shah, Faraaz A , Mellors, John W , Seheult, Jansen N. , Kitsios, Georgios D , Bain, William G

B57. CUTTING EDGE COVID RESEARCH | May 2, 2022 | Volume: No volume available | Issue: No issue available | Pages: A3144-A3144

10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a3144 Get It

Airway Mucus Plugs on CT Scan Are Associated with Worse Patient Reported Outcomes in Smokers with and Without COPD and No History of Exacerbations: A Cross Sectional Analysis of the COPDGene Study
Kim, V., Orejas, J. , Yen, A., Kligerman, S.J., Manapragada, Padma P. , Jacobs, K., Abozeed, Mostafa , Zahid, Mohd , Sonavane, S., Terry, Nina , Nath, H.P., Investigators, COPDGene, Kim, V., Dolliver, Wojciech Remington , Grumley, Scott , Yen, A.A., Kligerman, Seth , Aziz, M.A., Ahmed, Ali , Estépar, Raúl San Jośe , Díaz, Alejandro A.

A22. IMAGING AND MOLECULAR BIOMARKERS IN COPD | May 2, 2022 | Volume: No volume available | Issue: No issue available | Pages: A1076-A1076

10.1164/ajrccm-conference.2022.205.1_meetingabstracts.a1076 Get It

119 Current Practices in High and Low Volume Centers Regarding Corporotomy Localization During Penoscrotal Inflatable Penile Implant Surgery
Barnard, J, Renterghem, K. Van, Jacobs, B, Yafi, FA, Barnard, J, Barnard, J, Osmonov, Daniar , Ralph, David , Ziegelmann, Matthew , Wang, R, Kannady, Chris, Lentz, A, García, E. Lutz, Adrianne, R, Bettochi, Carlo, Hatzichristodoulou, G, Gross, Madeleine, Faix, A. , Otero, JR, Barnard, John Taylor , Barnard, J, Barnard, J, Barnard, J, Venturino, Luca , WANG, RY, Lentz, A, Adrianne, R., Hatzichristodoulou, Georgios , Martínez‐Salamanca, Juan Ignacio

The Journal of Sexual Medicine | April 26, 2022 | Volume: 19 | Issue: Supplement_1 | Pages: S60-S62

10.1016/j.jsxm.2022.01.383 Get It

ABSTRACT Introduction Literature concerning corporotomy location in multi-component inflatable penile prosthetic surgery via a penoscrotal approach is scarce if not non-existent. However, corporotomy location represents an important issue that may influence immediate and long-term outcomes regarding patient and partner satisfaction as well as device durability. Objective To report practices in low- and high-volume penile implant centers regarding corporotomy location. Methods Data from 18 (13 European and 5 American) implant centers were collected retrospectively between September 1st, 2018 and August 31st, 2019. Variables included: intraoperative proximal and distal corpus cavernosum length measurement, total corporal length measurement, total penile implant cylinder length, and length of rear tip extenders. Additionally, patient characteristics, indication for penile implant, operative time, type of implant utilized, reservoir characteristics and short term complications were reported. Results 809 virgin penile implant cases were included in the analysis. Mean age of participants was 61.5 +/- 9.6 years old. In total, 299 AMS 700TM (Boston Scientific) and 510 Coloplast Titan® devices were implanted. The mean proximal/distal corporal measurement ratio during corporotomy was 0.93 +/- 0.29. A statistically significant correlation between lower proximal /distal measurement ratio and higher age (p=0.0013), lower BMI (p<0.0001), use of rear tip extenders (RTE) (p=0.04), lower RTE length (p<0.0001) and absence of diabetes (p=0.0004) was reported. In a 3-month follow up period 49 complications and 37 revision procedures were reported. Conclusions This is the first study reporting and evaluating the current practices regarding corporotomy location during IPP placement in a multicenter cohort, particularly when including such a high number of patients. Nevertheless, the retrospective design limits the study outcomes. Even in experienced hands proximal length measurement in relation to distal length measurement in penoscrotal IPP surgery is in many cases sub-optimal, particularly when the tubing-cylinder connection of each device is taken into account. Disclosure No
Breast Cancer Screening Strategies for Women With ATM, CHEK2, and PALB2 Pathogenic Variants
Lowry, Kathryn P. , Geuzinge, H. Amarens , Stout, Natasha K. , Alagöz, Oğuzhan , Hampton, John M. , Koning, Harry J. de , Miglioretti, Diana L. , Ravesteyn, Nicolien T. van , Sprague, Brian L. , Tosteson, Anna N.A. , Weaver, Donald L. , Yaffe, Martin J. , Mandelblatt, Jeanne S. , Kurian, Allison W. , Auer, Paul L. , Berstein, Leslie, Carter, Brian D., Gaudet, Mia M. , Haiman, Christopher, Jacobs, Eric J. , John, Esther M. , Lindström, Sara , Martínez, Elena, Patel, Alpa V. , Reid, Sonya , Taylor, Jack A. , Teras, Lauren R., Vachon, Celine M. , Yao, Song, Ziogas, Argyrios, Goldgar, David E. , Chen, Chen , Chen, C , Miglioretti, Diana L , John, Esther M , Taylor, Jack A , de Koning, Harry J , Kurian, Allison W , Kerlikowske, Karla , Schechter, Clyde B. , Trentham‐Dietz, Amy , Yeh, Jennifer M. , Couch, Fergus J. , Hu, Chunling , Kraft, Peter , Polley, Eric C. , Robson, Mark E. , Hart, Steven N. , Nathanson, Katherine L. , Domchek, Susan M. , Ambrosone, Christine B. , Anton‐Culver, Hoda , Bandera, Elisa V. , Bertrand, Kimberly A. , Burnside, Elizabeth S. , Eliassen, A. Heather , Hodge, James M. , Hunter, David J. , Kooperberg, Charles , Lacey, James V. , Marchand, Loı̈c Le , Ma, Huiyan , Neuhausen, Susan L. , Newcomb, Polly A. , O’Brien, Katie M. , Olson, Janet E. , Ong, Irene M. , Pal, Tuya , Palmer, Julie R. , Rosenberg, Lynn A. , Sandler, Dale P. , Tamimi, Rulla M. , Teras, Lauren R. , Vachon, Celine M. , Weinberg, Clarice R. , Yadav, Siddhartha , Yao, Song , Weitzel, Jeffrey N.

JAMA Oncology | February 17, 2022 | Volume: 8 | Issue: 4 | Pages: 587

10.1001/jamaoncol.2021.6204 | PMID 35175286 Get It

Ibrutinib plus Obinutuzumab as Frontline Therapy for Chronic Lymphocytic Leukemia Is Associated with a Lower Rate of Infusion-Related Reactions and with Sustained Remissions after Ibrutinib Discontinuation: A Single-Arm, Open-Label, Phase 1b/2 Clinical Tri
Castro, Januario E. , Lengerke-Diaz, Paula A. , Luján, Juliana Vélez, Choi, Michael Y. , Moreno-Cortes, Eider , Forero-Forero, José Vicente , García-Robledo, Juan Esteban , Jacobs, C , McCarthy, Colin, Heinen, Alaina, Amaya-Chanaga, Carlos I., Moreno-Cortes, Eider F , Forero, Jose V , Jacobs, Chaja , Kipps, Thomas J , Castro, Januario E , Garcia-Robledo, Juan Esteban , Diaz, Paula A Lengerke , Kipps, Thomas J.

Advances in Hematology | January 22, 2022 | Volume: 2022 | Issue: No issue available | Pages: 1-8

10.1155/2022/4450824 | PMID 35103064 Get It

Ibrutinib-based therapies are costly and require continuous administration. We hypothesized combining BTK inhibition with anti-CD20 monoclonal antibodies would yield deep remissions allowing discontinuation. We enrolled 32 therapy-naïve CLL patients to receive ibrutinib plus obinutuzumab, followed by single-agent ibrutinib. Patients could discontinue ibrutinib after 36 months with sustained complete response (CR). We evaluated treatment safety, efficacy, and outcomes after ibrutinib discontinuation. The overall response rate was 100%, 28% achieved a CR, and 12.5% achieved bone marrow undetectable minimal residual disease. At a three-year median follow-up, 91% remain in remission with 100% overall survival. Five patients in sustained CR stopped ibrutinib and have not progressed. Eight non-CR patients discontinued for other reasons, with only two progressing. The treatment was safe, with a lower IRR rate. All patients responded to treatment with longer time-to-progression after discontinuation of ibrutinib. Our data support the evaluation of ibrutinib discontinuation strategies in more extensive clinical trials (https://Clinicaltrials.gov Identifier https://clinicaltrials.gov/ct2/show/NCT02315768).
The Importance of Accurately Defining Gender and Sex in Pathology
Jacobs, Jeremy W. , Lever, J.E. Peabody , Lee, Yeonsoo Sara , Bryan, Katherine M. , Booth, Garrett S. , Njoku, Ihuoma , Araj, Ellen, Lee, Yeonsoo S, Park, Jason Y , Sara Lee, Yeonsoo , Jacobs, Jeremy W , Booth, Garrett , Arvisais‐Anhalt, Simone , Park, Jason Y.

American Journal of Clinical Pathology | January 7, 2022 | Volume: 158 | Issue: 1 | Pages: 153-153

10.1093/ajcp/aqac008 | PMID 35150126 Get It

1063. ARGONAUT-V: Susceptibility of Multidrug-Resistant (MDR) Pseudomonas aeruginosa to Cefepime-Taniborbactam
Bethel, Christopher R. , Marshall, Steven H. , Fowler, Vance G. , Papp‐Wallace, Krisztina M. , Mack, Andrew R , Patel, Robin , van Duin, David , Fowler, Vance G. , Rhoads, Daniel D. , Jacobs, Michael R. , Akker, Focco van den , Six, David A. , Moeck, Greg , Bonomo, Robert A.

Open Forum Infectious Diseases | December 5, 2021 | Volume: 8 | Issue: Supplement_1 | Pages: S623-S624

10.1093/ofid/ofab466.1257 Get It

Abstract Background P. aeruginosa is a Gram-negative pathogen responsible for many serious infections. MDR, both intrinsic and acquired, presents major clinical challenges. Taniborbactam (formerly VNRX-5133; Fig 1) is a β-lactamase inhibitor (BLI) characterized as a bicyclic boronate, uniquely possessing activity toward all four Ambler classes of β-lactamases, both serine and metallo, with the exception of class B IMP β-lactamases. The β-lactam-BLI (BL-BLI) combination cefepime-taniborbactam (FTB; Fig 1) is currently in phase 3 clinical trials. Structures of taniborbactam and cefepime. The β-lactamase inhibitor is in red and the β-lactam antibiotic is in black. Methods The activity of FTB was tested against 197 well-characterized clinical P. aeruginosa isolates that were part of PRIMERS (Platforms for Rapid Identification of MDR-Gram-negative bacteria and Evaluation of Resistance Studies). Nearly 58% of these strains were reported as carbapenem-non-susceptible. Porin changes, efflux pumps, and/or the presence of acquired class A or class B carbapenemases were previously reported. Broth microdilution minimum inhibitory concentrations (MICs) were determined by CLSI M07 Ed. 11 methods with custom Sensititre frozen panels and interpreted using CLSI M100 Ed. 30 breakpoints. American Type Culture Collection strains were used for quality control. FEP breakpoints were provisionally used for FTB, where taniborbactam was fixed at 4 µg/mL. Results Percent susceptibility to BL agents alone was 45.2% for imipenem (IPM), 55.8% for meropenem (MEM), 60.9% for ceftazidime (CAZ), and 67.0% for FEP. The addition of BLI to BL increased % susceptibility for MEM-vaborbactam (MVB), 56.9%; ceftolozane-tazobactam (C/T), 77.7%, CAZ-avibactam (CZA), 79.7%, and FTB, 82.7%. MIC50s were in the susceptible range for all drugs except IPM, which was intermediate, and all MIC90s were in the resistant range (Table 1). Taniborbactam reduced FEP MIC by 2-fold in 32% of isolates and ≥ 4-fold in 13% of isolates. Against carbapenem-non-susceptible strains, % susceptibilities were: FTB, 68.5%, CZA, 63.0%, C/T, 59.3%; and MVB, 21.3% (Table 2). MIC50 and MIC90 values (µg/mL) and percent susceptibility (%S) for all P. aeruginosa strains (n=197). AMK, amikacin; ATM, aztreonam; C/T, ceftolozane-tazobactam; CAZ, ceftazidime; CZA, ceftazidime-avibactam; FEP, cefepime; FTB, cefepime-taniborbactam; IPM, imipenem; MEM, meropenem; MVB, meropenem-vaborbactam; TZP, piperacillin-tazobactam; TOB, tobramycin. *The breakpoints for FEP and MEM alone were provisionally applied to FTB and MVB, respectively. Tazobactam, avibactam, and taniborbactam were fixed at 4 µg/mL, while vaborbactam was fixed at 8 µg/mL. Breakpoints from CLSI M100, 31st ed, 2021. MIC50 and MIC90 values (µg/mL) and percent susceptibility (%S) for the subset of carbapenem-non-susceptible P. aeruginosa strains (n=108). AMK, amikacin; ATM, aztreonam; C/T, ceftolozane-tazobactam; CAZ, ceftazidime; CZA, ceftazidime-avibactam; FEP, cefepime; FTB, cefepime-taniborbactam; IPM, imipenem; MEM, meropenem; MVB, meropenem-vaborbactam; TZP, piperacillin-tazobactam; TOB, tobramycin. *The breakpoints for FEP and MEM alone were provisionally applied to FTB and MVB, respectively. Tazobactam, avibactam, and taniborbactam were fixed at 4 µg/mL, while vaborbactam was fixed at 8 µg/mL. Breakpoints from CLSI M100, 31st ed, 2021. Conclusion Compared to MVB, CZA, and C/T, FTB demonstrated the greatest activity against the 197 P. aeruginosa strains tested, including many carbapenem-non-susceptible strains. Pending completion of clinical development, FTB may be a promising therapeutic option for MDR P. aeruginosa infections. Disclosures Robin Patel, MD, 1928 Diagnostics (Consultant)BioFire Diagnostics (Grant/Research Support)ContraFect Corporation (Grant/Research Support)Curetis (Consultant)Hylomorph AG (Grant/Research Support)IDSA (Other Financial or Material Support, Editor’s Stipend)Infectious Diseases Board Review Course (Other Financial or Material Support, Honoraria)Mammoth Biosciences (Consultant)NBME (Other Financial or Material Support, Honoraria)Netflix (Consultant)Next Gen Diagnostics (Consultant)PathoQuest (Consultant)PhAST (Consultant)Qvella (Consultant)Samsung (Other Financial or Material Support, Patent Royalties)Selux Diagnostics (Consultant)Shionogi & Co., Ltd. (Grant/Research Support)Specific Technologies (Consultant)TenNor Therapeutics Limited (Grant/Research Support)Torus Biosystems (Consultant)Up-to-Date (Other Financial or Material Support, Honoraria) Robin Patel, MD, BioFire (Individual(s) Involved: Self): Grant/Research Support; Contrafect (Individual(s) Involved: Self): Grant/Research Support; IDSA (Individual(s) Involved: Self): Editor’s stipend; NBME, Up-to-Date and the Infectious Diseases Board Review Course (Individual(s) Involved: Self): Honoraria; Netflix (Individual(s) Involved: Self): Consultant; TenNor Therapeutics Limited (Individual(s) Involved: Self): Grant/Research Support; to Curetis, Specific Technologies, Next Gen Diagnostics, PathoQuest, Selux Diagnostics, 1928 Diagnostics, PhAST, Torus Biosystems, Mammoth Biosciences and Qvella (Individual(s) Involved: Self): Consultant David van Duin, MD, PhD, Entasis (Advisor or Review Panel member)genentech (Advisor or Review Panel member)Karius (Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Pfizer (Consultant, Advisor or Review Panel member)Qpex (Advisor or Review Panel member)Shionogi (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member)Utility (Advisor or Review Panel member) Vance G. Fowler, Jr., MD, MHS, Achaogen (Consultant)Advanced Liquid Logics (Grant/Research Support)Affinergy (Consultant, Grant/Research Support)Affinium (Consultant)Akagera (Consultant)Allergan (Grant/Research Support)Amphliphi Biosciences (Consultant)Aridis (Consultant)Armata (Consultant)Basilea (Consultant, Grant/Research Support)Bayer (Consultant)C3J (Consultant)Cerexa (Consultant, Other Financial or Material Support, Educational fees)Contrafect (Consultant, Grant/Research Support)Debiopharm (Consultant, Other Financial or Material Support, Educational fees)Destiny (Consultant)Durata (Consultant, Other Financial or Material Support, educational fees)Genentech (Consultant, Grant/Research Support)Green Cross (Other Financial or Material Support, Educational fees)Integrated Biotherapeutics (Consultant)Janssen (Consultant, Grant/Research Support)Karius (Grant/Research Support)Locus (Grant/Research Support)Medical Biosurfaces (Grant/Research Support)Medicines Co. (Consultant)MedImmune (Consultant, Grant/Research Support)Merck (Grant/Research Support)NIH (Grant/Research Support)Novadigm (Consultant)Novartis (Consultant, Grant/Research Support)Pfizer (Grant/Research Support)Regeneron (Consultant, Grant/Research Support)sepsis diagnostics (Other Financial or Material Support, Pending patent for host gene expression signature diagnostic for sepsis.)Tetraphase (Consultant)Theravance (Consultant, Grant/Research Support, Other Financial or Material Support, Educational fees)Trius (Consultant)UpToDate (Other Financial or Material Support, Royalties)Valanbio (Consultant, Other Financial or Material Support, Stock options)xBiotech (Consultant) Daniel D. Rhoads, MD, Becton, Dickinson and Company (Grant/Research Support) Michael Jacobs, MBBS, Venatorx Pharmaceuticals, Inc. (Grant/Research Support) Focco van den Akker, PhD, Venatorx Pharmaceuticals, Inc. (Grant/Research Support) David A. Six, PhD, Venatorx Pharmaceuticals, Inc. (Employee) Greg Moeck, PhD, Venatorx Pharmaceuticals, Inc. (Employee) Krisztina M. Papp-Wallace, Ph.D., Merck & Co., Inc. (Grant/Research Support)Spero Therapeutics, Inc. (Grant/Research Support)Venatorx Pharmaceuticals, Inc. (Grant/Research Support)Wockhardt Ltd. (Other Financial or Material Support, Research Collaborator) Robert A. Bonomo, MD, entasis (Research Grant or Support)Merck (Grant/Research Support)NIH (Grant/Research Support)VA Merit Award (Grant/Research Support)VenatoRx (Grant/Research Support)
1055. ARGONAUT-IV: Susceptibility of Carbapenem-resistant Klebsiellae to Ceftibuten/VNRX-5236
Bethel, Christopher R. , Marshall, Steven H. , Fowler, Vance G. , Papp‐Wallace, Krisztina M. , Mack, Andrew R , Patel, Robin , van Duin, David , Fowler, Vance G. , Rhoads, Daniel D. , Jacobs, Michael R. , Akker, Focco van den , Six, David A. , Moeck, Greg , Bonomo, Robert A.

Open Forum Infectious Diseases | December 5, 2021 | Volume: 8 | Issue: Supplement_1 | Pages: S619-S620

10.1093/ofid/ofab466.1249 Get It

Abstract Background Carbapenem resistance in Klebsiellae spp. arises through mutational and acquired mechanisms and is considered an “urgent threat” by the CDC. VNRX-5236 is a bicyclic boronate β-lactamase inhibitor (BLI) that combines oral bioavailability (via etzadroxil prodrug VNRX-7145; Figure 1) and activity against all three Ambler classes of serine β-lactamases. VNRX-7145 is currently in development with the oral cephalosporin, ceftibuten (CTB) (Figure 1). Figure 1. Structures of VNRX-7145, VNRX-5236, and ceftibuten. The β-lactamase inhibitors are in red and the β-lactam antibiotic is in black. Methods The activity of CTB/VNRX-5236 against 200 carbapenem-resistant Klebsiellae from the Consortium on Resistance against Carbapenems in Klebsiella (CRACKLE) was assessed in this study. Among these, 193 expressed class A KPC enzymes, one expressed a class B NDM enzyme, and six expressed a class D OXA-48 or variant enzyme. Minimum inhibitory concentrations (MIC) were determined by broth microdilution (CLSI M07 Ed. 11) using the ThermoFisher Sensititre system with custom assay panels. MICs were interpreted using CLSI M100 Ed. 30, except the EUCAST breakpoint for CTB (S≤1 µg/mL) was used for CTB and was applied for comparative purposes to CTB/VNRX-5236 MICs where VNRX-5236 was fixed at 4 µg/mL. American Type Culture Collection strains were used for quality control. Results 92.5% of stains studied in this CRACKLE collection were provisionally susceptible to CTB/VNRX-5236. In comparison, strains were 95.5% and 98% susceptible to meropenem-vaborbactam (MVB) and ceftazidime-avibactam (CZA), respectively. MIC50s were in the susceptible range for CZA, MVB, and CTB/VNRX-5236; and resistant for CTB, ceftazidime (CAZ) and meropenem (MEM). MIC90s were in the susceptible range for CZA, MVB, and CTB/VNRX-5236 and resistant range for CAZ, MEM, and CTB (Table 1). One of four CZA-resistant and three of nine MVB non-susceptible strains were provisionally susceptible to CTB/VNRX-5236. MIC50 and MIC90 values (µg/mL) and percent susceptibility for Klebsiella pneumoniae strains (n=200). AMK, amikacin; CST, colistin; CAZ, ceftazidime; CZA, ceftazidime-avibactam; FEP, cefepime; MEM, meropenem; MVB, meropenem-vaborbactam; CTB, ceftibuten; TGC, tigecycline. * The breakpoint for CST is intermediate, as no susceptible breakpoint is available. ** The CTB breakpoint is valid only for urinary tract isolates. *** The breakpoint for CTB was provisionally used for CTB/VNRX-5236, where VNRX-5236 was fixed at 4 µg/mL. Conclusion The addition of VNRX-5236 enhanced the activity of CTB against the 200 Klebsiella isolates tested, reaching a total of 92.5% susceptibility. The prodrug (VNRX-7145) allows for oral administration, making it a potential option for step-down therapy. Importantly, VNRX-5236 has a broader spectrum of activity than existing oral BLIs, opening new treatment options for resistant infections as a key addition to the existing antibiotic arsenal. Disclosures Robin Patel, MD, 1928 Diagnostics (Consultant)BioFire Diagnostics (Grant/Research Support)ContraFect Corporation (Grant/Research Support)Curetis (Consultant)Hylomorph AG (Grant/Research Support)IDSA (Other Financial or Material Support, Editor’s Stipend)Infectious Diseases Board Review Course (Other Financial or Material Support, Honoraria)Mammoth Biosciences (Consultant)NBME (Other Financial or Material Support, Honoraria)Netflix (Consultant)Next Gen Diagnostics (Consultant)PathoQuest (Consultant)PhAST (Consultant)Qvella (Consultant)Samsung (Other Financial or Material Support, Patent Royalties)Selux Diagnostics (Consultant)Shionogi & Co., Ltd. (Grant/Research Support)Specific Technologies (Consultant)TenNor Therapeutics Limited (Grant/Research Support)Torus Biosystems (Consultant)Up-to-Date (Other Financial or Material Support, Honoraria) Robin Patel, MD, BioFire (Individual(s) Involved: Self): Grant/Research Support; Contrafect (Individual(s) Involved: Self): Grant/Research Support; IDSA (Individual(s) Involved: Self): Editor’s stipend; NBME, Up-to-Date and the Infectious Diseases Board Review Course (Individual(s) Involved: Self): Honoraria; Netflix (Individual(s) Involved: Self): Consultant; TenNor Therapeutics Limited (Individual(s) Involved: Self): Grant/Research Support; to Curetis, Specific Technologies, Next Gen Diagnostics, PathoQuest, Selux Diagnostics, 1928 Diagnostics, PhAST, Torus Biosystems, Mammoth Biosciences and Qvella (Individual(s) Involved: Self): Consultant David van Duin, MD, PhD, Entasis (Advisor or Review Panel member)genentech (Advisor or Review Panel member)Karius (Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Pfizer (Consultant, Advisor or Review Panel member)Qpex (Advisor or Review Panel member)Shionogi (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member)Utility (Advisor or Review Panel member) Vance G. Fowler, Jr., MD, MHS, Achaogen (Consultant)Advanced Liquid Logics (Grant/Research Support)Affinergy (Consultant, Grant/Research Support)Affinium (Consultant)Akagera (Consultant)Allergan (Grant/Research Support)Amphliphi Biosciences (Consultant)Aridis (Consultant)Armata (Consultant)Basilea (Consultant, Grant/Research Support)Bayer (Consultant)C3J (Consultant)Cerexa (Consultant, Other Financial or Material Support, Educational fees)Contrafect (Consultant, Grant/Research Support)Debiopharm (Consultant, Other Financial or Material Support, Educational fees)Destiny (Consultant)Durata (Consultant, Other Financial or Material Support, educational fees)Genentech (Consultant, Grant/Research Support)Green Cross (Other Financial or Material Support, Educational fees)Integrated Biotherapeutics (Consultant)Janssen (Consultant, Grant/Research Support)Karius (Grant/Research Support)Locus (Grant/Research Support)Medical Biosurfaces (Grant/Research Support)Medicines Co. (Consultant)MedImmune (Consultant, Grant/Research Support)Merck (Grant/Research Support)NIH (Grant/Research Support)Novadigm (Consultant)Novartis (Consultant, Grant/Research Support)Pfizer (Grant/Research Support)Regeneron (Consultant, Grant/Research Support)sepsis diagnostics (Other Financial or Material Support, Pending patent for host gene expression signature diagnostic for sepsis.)Tetraphase (Consultant)Theravance (Consultant, Grant/Research Support, Other Financial or Material Support, Educational fees)Trius (Consultant)UpToDate (Other Financial or Material Support, Royalties)Valanbio (Consultant, Other Financial or Material Support, Stock options)xBiotech (Consultant) Daniel D. Rhoads, MD, Becton, Dickinson and Company (Grant/Research Support) Michael Jacobs, MBBS, Venatorx Pharmaceuticals, Inc. (Grant/Research Support) Focco van den Akker, PhD, Venatorx Pharmaceuticals, Inc. (Grant/Research Support) David A. Six, PhD, Venatorx Pharmaceuticals, Inc. (Employee) Greg Moeck, PhD, Venatorx Pharmaceuticals, Inc. (Employee) Krisztina M. Papp-Wallace, Ph.D., Merck & Co., Inc. (Grant/Research Support)Spero Therapeutics, Inc. (Grant/Research Support)Venatorx Pharmaceuticals, Inc. (Grant/Research Support)Wockhardt Ltd. (Other Financial or Material Support, Research Collaborator) Robert A. Bonomo, MD, entasis (Research Grant or Support)Merck (Grant/Research Support)NIH (Grant/Research Support)VA Merit Award (Grant/Research Support)VenatoRx (Grant/Research Support)
133. ARGONAUT-III: Susceptibility of Carbapenem-resistant Klebsiellae to Cefepime-Taniborbactam
Bethel, Christopher R. , Marshall, Steven, Fowler, Vance G. , Papp‐Wallace, Krisztina M. , Mack, Andrew R , Patel, Robin , van Duin, David , Fowler, Vance G. , Rhoads, Daniel D. , Jacobs, Michael R. , Akker, Focco van den , Six, David A. , Moeck, Greg , Bonomo, Robert A.

Open Forum Infectious Diseases | December 5, 2021 | Volume: 8 | Issue: Supplement_1 | Pages: S81-S82

10.1093/ofid/ofab466.133 Get It

Abstract Background Klebsiellae are Gram-negative pathogens responsible for serious nosocomial and community-acquired infections. Carbapenem resistance, both intrinsic and acquired, complicates therapy. Taniborbactam (formerly VNRX-5133; Fig 1) is a bicyclic boronate β-lactamase inhibitor (BLI) that inhibits all four Ambler classes of β-lactamase enzymes, both serine- and metallo-, with the notable exception of class B IMP β-lactamases. Taniborbactam is currently undergoing phase 3 clinical trials in combination with cefepime (FEP; Fig 1) as part of the β-lactam-BLI (BL-BLI) combination FEP-taniborbactam (FTB). Figure 1. Structures of taniborbactam and cefepime. The β-lactamase inhibitor is in red and the β-lactam antibiotic is in black. Methods We determined the activity of FTB against 200 carbapenem-resistant Klebsiellae (CRK) strains collected as part of the Antibiotic Resistance Leadership Group (ARLG) Consortium on Resistance against Carbapenems in Klebsiella (CRACKLE) study. Among these strains, 193 expressed class A KPCs, one expressed a class B NDM, and six expressed class D OXA-48 or variants. Broth microdilution minimum inhibitory concentrations (MIC)s were determined using the ThermoFisher Sensititre system with custom assay panels. American Type Culture Collection strains were used for quality control. The susceptible-dose-dependent breakpoint for FEP was provisionally used for FTB, where taniborbactam was fixed at 4 µg/mL. Results Among the 200 Klebsiella strains tested, susceptibility for β-lactams alone ranged from 1% for ceftazidime (CAZ), 2.5% for meropenem, and 13.5% for FEP (Table 1). The addition of BLIs increased % susceptibility compared to BL alone to: 98% for CAZ-avibactam (CZA); 95.5% for MEM-vaborbactam (MVB); and 99.0% for FTB. MIC50 and MIC90 were in the susceptible and provisionally susceptible range for CZA and MVB, and in the provisionally susceptible range for FTB. Analyzing the CZA and MVB non-susceptible strains, 7 of 9 MVB non-susceptible strains and 2 of 4 CZA-resistant strains were provisionally susceptible to FTB. Table 1. MIC50 and MIC90 values (μg/mL) and percent susceptibility for Klebsiella pneumoniae strains (n=200). AMK, amikacin; CST, colistin; CAZ, ceftazidime; CZA, ceftazidime-avibactam; FEP, cefepime; FTB, cefepime-taniborbactam; MEM, meropenem; MVB, meropenem-vaborbactam; TGC, tigecycline. * The breakpoint for CST is intermediate, as no susceptible breakpoint is available. ** The susceptible-dose-dependent breakpoint for FEP alone was provisionally applied to FTB, where taniborbactam was fixed at 4 μg/mL. Breakpoints from CLSI M100, 31st ed, 2021. Conclusion The addition of taniborbactam restored susceptibility to FEP in 99.0% of CRACKLE isolates studied, comparable to CZA and MVB. Taniborbactam also restored FEP activity against some MVB- and CZA-resistant strains. FTB may provide a promising therapy for CRK infections. Disclosures Robin Patel, MD, 1928 Diagnostics (Consultant)BioFire Diagnostics (Grant/Research Support)ContraFect Corporation (Grant/Research Support)Curetis (Consultant)Hylomorph AG (Grant/Research Support)IDSA (Other Financial or Material Support, Editor’s Stipend)Infectious Diseases Board Review Course (Other Financial or Material Support, Honoraria)Mammoth Biosciences (Consultant)NBME (Other Financial or Material Support, Honoraria)Netflix (Consultant)Next Gen Diagnostics (Consultant)PathoQuest (Consultant)PhAST (Consultant)Qvella (Consultant)Samsung (Other Financial or Material Support, Patent Royalties)Selux Diagnostics (Consultant)Shionogi & Co., Ltd. (Grant/Research Support)Specific Technologies (Consultant)TenNor Therapeutics Limited (Grant/Research Support)Torus Biosystems (Consultant)Up-to-Date (Other Financial or Material Support, Honoraria) Robin Patel, MD, BioFire (Individual(s) Involved: Self): Grant/Research Support; Contrafect (Individual(s) Involved: Self): Grant/Research Support; IDSA (Individual(s) Involved: Self): Editor’s stipend; NBME, Up-to-Date and the Infectious Diseases Board Review Course (Individual(s) Involved: Self): Honoraria; Netflix (Individual(s) Involved: Self): Consultant; TenNor Therapeutics Limited (Individual(s) Involved: Self): Grant/Research Support; to Curetis, Specific Technologies, Next Gen Diagnostics, PathoQuest, Selux Diagnostics, 1928 Diagnostics, PhAST, Torus Biosystems, Mammoth Biosciences and Qvella (Individual(s) Involved: Self): Consultant David van Duin, MD, PhD, Entasis (Advisor or Review Panel member)genentech (Advisor or Review Panel member)Karius (Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Pfizer (Consultant, Advisor or Review Panel member)Qpex (Advisor or Review Panel member)Shionogi (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member)Utility (Advisor or Review Panel member) Vance G. Fowler, Jr., MD, MHS, Achaogen (Consultant)Advanced Liquid Logics (Grant/Research Support)Affinergy (Consultant, Grant/Research Support)Affinium (Consultant)Akagera (Consultant)Allergan (Grant/Research Support)Amphliphi Biosciences (Consultant)Aridis (Consultant)Armata (Consultant)Basilea (Consultant, Grant/Research Support)Bayer (Consultant)C3J (Consultant)Cerexa (Consultant, Other Financial or Material Support, Educational fees)Contrafect (Consultant, Grant/Research Support)Debiopharm (Consultant, Other Financial or Material Support, Educational fees)Destiny (Consultant)Durata (Consultant, Other Financial or Material Support, educational fees)Genentech (Consultant, Grant/Research Support)Green Cross (Other Financial or Material Support, Educational fees)Integrated Biotherapeutics (Consultant)Janssen (Consultant, Grant/Research Support)Karius (Grant/Research Support)Locus (Grant/Research Support)Medical Biosurfaces (Grant/Research Support)Medicines Co. (Consultant)MedImmune (Consultant, Grant/Research Support)Merck (Grant/Research Support)NIH (Grant/Research Support)Novadigm (Consultant)Novartis (Consultant, Grant/Research Support)Pfizer (Grant/Research Support)Regeneron (Consultant, Grant/Research Support)sepsis diagnostics (Other Financial or Material Support, Pending patent for host gene expression signature diagnostic for sepsis.)Tetraphase (Consultant)Theravance (Consultant, Grant/Research Support, Other Financial or Material Support, Educational fees)Trius (Consultant)UpToDate (Other Financial or Material Support, Royalties)Valanbio (Consultant, Other Financial or Material Support, Stock options)xBiotech (Consultant) Daniel D. Rhoads, MD, Becton, Dickinson and Company (Grant/Research Support) Michael Jacobs, MBBS, Venatorx Pharmaceuticals, Inc. (Grant/Research Support) Focco van den Akker, PhD, Venatorx Pharmaceuticals, Inc. (Grant/Research Support) David A. Six, PhD, Venatorx Pharmaceuticals, Inc. (Employee) Greg Moeck, PhD, Venatorx Pharmaceuticals, Inc. (Employee) Krisztina M. Papp-Wallace, Ph.D., Merck & Co., Inc. (Grant/Research Support)Spero Therapeutics, Inc. (Grant/Research Support)Venatorx Pharmaceuticals, Inc. (Grant/Research Support)Wockhardt Ltd. (Other Financial or Material Support, Research Collaborator) Robert A. Bonomo, MD, entasis (Research Grant or Support)Merck (Grant/Research Support)NIH (Grant/Research Support)VA Merit Award (Grant/Research Support)VenatoRx (Grant/Research Support)